Kurakata S, Tomatsu M, Arai M, Arai H, Hishinuma A, Kohno H, Kitamura K, Kobayashi T, Nomoto K
Bio-Science Research Laboratories, Sankyo Co. Ltd., Tokyo, Japan.
Cancer Immunol Immunother. 1991;33(2):71-9. doi: 10.1007/BF01742532.
RS-0481, (4R)-3-benzoyl-N-[(1R)-phenylethyl]-4-thiazolidinecarboxamide, is a compound that can re-establish the function of certain lymphoid cell populations impaired by the presence of a growing tumor in an animal. The compound markedly augmented the tumor-specific cytotoxic T lymphocytes, TDTH (delayed-type hypersensitivity T cells), and the nonspecific lymphokine-activated-killer-cell-like cell responses. It also enhanced the tumor-inhibitory effect of macrophages in tumor-bearing mice, but not in normal mice, indicating that it enhances the antitumor immune responses. Lymphocytes from RS-0481-treated tumor-bearing mice released significantly higher amounts of macrophage-activating factor(s) (MAF) and interleukin-2(IL-2)-like factors in culture compared with lymphocytes from untreated animals. Also, sera from treated tumor bearers showed elevated colony-stimulating factor (CSF) activity. Although the compound did not influence the factor-producing activity in mice without tumor, it enhanced the responsiveness of their bone marrow cells, T cells, and macrophages to CSF, IL-2, and MAF. It seems therefore possible that the compound enhances the responsiveness of immunocompetent cells to cytokines, resulting in a marked augmentation of antitumor T cell responses in tumor-bearing mice. Consistently it inhibited the development of lymph node metastasis of transplanted X5563 plasmacytoma, and we showed that T cells play a decisive role in this inhibition. The compound also counteracted the development of suppressor T cell activity in the spleen of tumor-bearing mice.
RS - 0481，即(4R)-3-苯甲酰基-N-[(1R)-苯乙基]-4-噻唑烷甲酰胺，是一种能够恢复动物体内因肿瘤生长而受损的某些淋巴细胞群体功能的化合物。该化合物显著增强了肿瘤特异性细胞毒性T淋巴细胞、迟发型超敏反应T细胞（TDTH）以及非特异性淋巴因子激活的杀伤细胞样细胞反应。它还增强了荷瘤小鼠巨噬细胞的肿瘤抑制作用，但对正常小鼠没有这种作用，这表明它增强了抗肿瘤免疫反应。与未处理动物的淋巴细胞相比，来自经RS - 0481处理的荷瘤小鼠的淋巴细胞在培养物中释放出显著更多的巨噬细胞激活因子和白细胞介素-2样因子。此外，经处理的荷瘤动物的血清显示集落刺激因子（CSF）活性升高。虽然该化合物对无肿瘤小鼠的因子产生活性没有影响，但它增强了其骨髓细胞、T细胞和巨噬细胞对CSF、白细胞介素-2和巨噬细胞激活因子的反应性。因此，该化合物似乎有可能增强免疫活性细胞对细胞因子的反应性，从而导致荷瘤小鼠的抗肿瘤T细胞反应显著增强。一致的是，它抑制了移植的X5563浆细胞瘤淋巴结转移的发生，并且我们表明T细胞在这种抑制中起决定性作用。该化合物还对抗了荷瘤小鼠脾脏中抑制性T细胞活性的发展。
